Pulmonary immaturity in prematurely born infants remains a leading cause of neonatal mortality and morbidity. At least two functions important for the fetal lung to make the transition to an organ of gas exchange as a neonate are linked to Beta-adrenergic response. B-adrenergic agonists stimulate the release and synthesis of surface active material and the removal of fluid from alveolae. In our experiments we will test the role of endogenous adrenergic factors in these functions by administering an irreversible Beta-adrenergic antagonist to rabbit fetuses before birth and correlating release and synthesis of saturated phosphatidylcholine (SPC), lung water content and Beta-adrenergic receptor concentration at different times shortly after birth. We will study in detail the relationship between occupancy of Beta-adrenergic receptor, adylate cyclase activation, cAMP generation and release of SPC using both intact animals and organ culture of lung. We have previously reported that glucocorticoids increase Beta-receptor concentrations precociously in homogenates of fetal lung. We will also use the organ culture system to determine the mechanism of this glucocorticoid effect. We will use autoradiography to determine if this effect of increasing receptors occurs preferentially in alveolar cells. We have also recently demonstrated that glucocorticoids accelerate a developmental increase of coupling of Beta-receptor occupancy to response, manifest as an increase in high affinity agonist binding. We will use organ culture to determine glucocorticoid mechanism. We will determine if this change is similar to the developmental change by detailed analysis of components of the Beta-receptor adenylate cyclase system. Qualitative and semiquantitative analysis of the coupling protein(s) (N) in particulate from treated and different aged petuses will be performed by inserting N from these membranes into S49 cyc- mutant cells and by performing SDS gels of these membranes after cholera toxin stimulated ADP32 ribosylation. In addition we will use many of these techniques, including radioautography, to examine sex differences in Beta-receptor, receptor coupling and response to attempt to explain the increased morbidity in male neonates.